In the United States, people infected with the human
immunodeficiency virus (HIV) drink more alcohol than people in the
general population. Specifically, a higher proportion drink risky
amounts (1) or have an alcohol use disorder (i.e., abuse or dependence)
(Conigliaro et al. 2003; Galvan et al. 2002; Lefevre et al. 1995; Samet
et al. 2003a,b, 2004). Risky alcohol use in HIV-infected people has been
associated with the following range of adverse effects:

Given the spectrum of problems associated with such alcohol use
among HIV-infected patients, one important avenue to improving the
health of this population is to develop interventions that target
alcohol use and its associated consequences. Accordingly, interventions
have been designed to both decrease alcohol consumption and address the
specific adverse health consequences.

The concept that negative consequences of alcohol use can be
reduced in patients with HIV infection is based on research
demonstrating the impact of clinical interventions on alcohol
consumption and associated negative consequences in patients without HIV
infection (Institute of Medicine 1990; Kristenson et al. 1983). Alcohol
research over the past three decades has demonstrated that behavioral
interventions can be effective, with benefits varying based on setting,
severity of alcohol problems, and patient characteristics. For example,
meta-analyses of randomized controlled trials (RCTs) (2) of
interventions to reduce risky alcohol use demonstrated decreased
drinking for patients in primary care settings (Beich et al. 2003; Kaner
et al. 2007). However, no such effects were found in meta-analyses of
interventions delivered in hospital settings (Emmen et al. 2004),
possibly because inpatients typically have greater severity of alcohol
problems (i.e., most are alcohol dependent) (Saitz et al. 2007, 2008).
Several high-quality RCTs of brief interventions delivered in emergency
departments also detected no or limited benefit (D'Onofrio and
Degutis 2002; Daeppen et al. 2007; Longabaugh et al. 2001; Monti et al.
1999). The influence of the patient's consumption levels also was
demonstrated in several studies. For example, in two separate RCTs in
the primary-care setting (Fleming et al. 1997; Ockene et al. 1999),
where patients were seeking medical care but not necessarily for an
alcohol problem, implementation of a 5- to 15-minute discussion reduced
alcohol consumption in patients who met the criteria for risky drinking.
Studies of such brief interventions among patients who met the criteria
for alcohol dependence, however, have shown no benefit (Kaner et al.
2007; Whitlock et al. 2004; Wutzke et al. 2002).

Given the strong evidence that alcohol consumption is an important
health issue for many people with HIV infection, efforts to potentially
ameliorate these problems by addressing alcohol use are of great
interest. The studies in non-HIV-infected people reviewed above suggest
that interventions among HIV-infected people with alcohol problems could
be beneficial. However, the wide range of results in these intervention
studies based on setting and disease severity argues for the need to
carefully assess efforts to mitigate alcohol's deleterious impact
on health in HIV-infected patients. As an important step in this
direction, this article summarizes the findings of a review of the
clinical trial literature on interventions addressing alcohol
consumption and its consequences among HIV-infected patients. After
describing the design of the literature search and evaluation, the
article reviews the findings of the studies identified and discusses the
implications of those findings.

DESIGN OF THE LITERATURE REVIEW

The literature review sought to identify clinical trials of
interventions among ' HIV-infected people with past or current
unhealthy alcohol use (i.e., the spectrum from risky drinking to alcohol
dependence [Saitz 2005]) that reported effects on any of the following
outcomes:

* HIV disease progression;

* Receipt of HIV treatment;

* HIV medication adherence;

* HIV risk behaviors;

* Acquisition of sexually transmitted infections; and

* Alcohol use.

To be included in the review, the studies had to report
alcohol-specific outcomes. Beyond that, the studies were classified into
three categories of specificity. The most specific category comprised
clinical trials that included only HIV-infected people with past or
current unhealthy alcohol use. The second category comprised clinical
trials that included only HIV-infected people but in which not all of
the participants exhibited unhealthy alcohol use. For a study to be
included in this category, at least 10 percent of participants had to
report current alcohol use. The third category of studies comprised
trials that were aimed at preventing alcohol use and sexual behaviors
that put people at risk of HIV infection among alcohol-using people.
Although these studies did not include HIV-infected participants or did
not report the HIV status of the participants, they were reviewed
because they may inform future research on people at risk of HIV
transmission in the setting of alcohol use.

Initially, the review intended to include only RCTs. However, very
few studies were identified that met this criterion in the first two
categories. Therefore, the search was expanded to include nonrandomized
and non-controlled clinical intervention trials in categories 1 and 2.

To identify relevant studies, the literature database MEDLINE was
searched through September 30, 2009, using the search terms "HIV
alcohol, hazardous drinking, risky drinking, problem drinking,
counseling, brief intervention, 12 step, pharmacotherapy, naltrexone,
acamprosate, disulfiram, topiramate, and clinical trial." For all
articles identified using this approach, the reference lists also were
scanned, as were related articles identified by the search engine for
the MEDLINE data base to look for additional studies. Reference lists
for articles that were closely related, but did not meet the criteria,
also were reviewed. Finally, articles referenced in relevant review
articles were examined. Titles of all articles were reviewed to
determine if the articles met the selection criteria. If the nature of
the study could not be discerned through the title, the abstract and/or
full text of the article was retrieved and reviewed.

For all studies that met the criteria for one of the three
categories, information on the setting, study design, methodological
quality, type of intervention, outcomes reported, period of follow-up,
and results was extracted. The following sections summarize the findings
of these analyses. They are presented as a descriptive narrative
synthesis because studies were too few and heterogeneous to perform a
standard meta-analysis.

RESULTS OF THE LITERATURE REVIEW

The search strategy described above identified 241 potentially
relevant studies that were evaluated further. Of these, four studies
including a total of 578 patients (Aharonovich et al. 2006; Parsons et
al. 2007; Samet et al. 2005; Velasquez et al. 2009) met the selection
criteria for the first category (see table 1). Another five clinical
trials that included 1,311 patients (Gilbert et al. 2008; Naar-King et
al. 2006, 2008; Rotheram-Borus et al. 2001, 2009; Sorensen et al. 2003)
fell into the second category. In addition, two informative studies of
interventions among people at high-risk for HIV reported outcomes
specific to alcohol use (Kalichman et al. 2008; Morgenstern et al.
2007). All of these studies are reviewed below. Some other studies that
involved alcohol-using, HIV-infected patients, but were excluded from
this discussion because of serious design or methodological limitations,
are listed in Table 2 because they may inform additional research.
Interestingly, no controlled trials of the four medications recommended
by NIAAA (2007) for the treatment of alcohol dependence (i.e.,
disulfiram, naltrexone, acamprosate, and topiramate) have been conducted
in HIV-infected patients.

CLINICAL TRIALS AMONG HIV-INFECTED PEOPLE WITH PAST OR CURRENT
UNHEALTHY ALCOHOL USE

Velasquez and Colleagues (2009) Study. These investigators
conducted an RCT among 253 HIV-infected men who had had sex with men in
the previous 3 months and who scored more than eight points on the AUDIT
questionnaire (Babor et al. 2001). The intervention group received four
manual-guided individual sessions and four manual-guided peer education
and support group sessions that utilized motivational interviewing (MI)
counseling strategies (Miller and Rollnick 2002) to guide participants
through the stages of change of Prochaska and DiClemente's
Trans-Theoretical Model (3) (Prochaska and DiClemente 1982). In
contrast, the control group received educational materials on HIV and
alcohol, referral information, and advice to stop or cut back on their
alcohol use. At the 12-month follow-up, the investigators determined
some benefits of the intervention on some of the measures evaluated. For
example, the control group had 1.4 times the number of drinks per 30
days and 1.5 times the number of heavy-drinking days per 30 days
compared with the intervention group. For other measures (e.g., having
anal sex without a condom, number of drinking days, or number of days on
which both drinking and sex occurred), however, no significant
difference existed between the two groups. Only when the analysis of
same-day drinking and sex was restricted to participants who had shown
this behavior at baseline, did those in the control group have
significantly (i.e., 2.19 times) more days on which drinking and sex
occurred than the intervention group. The interpretation of these
findings is limited by the fact that there was differential loss to
follow-up--that is, the analyses included only 81 percent of
participants randomized to the intervention group and 90 percent of
subjects randomized to the control group. Thus, one cannot exclude the
possibility that particularly in the intervention group, participants
with worse outcomes were not included in the analysis.

Aharonovich and Colleagues (2006) Study In this pilot study, 31
HIV-infected primary-care patients with heavy alcohol use received one
session of MI from a trained counselor, followed by daily
telephone-based interactive voice response (IVR) assessments of drinking
amounts and graphic feedback of changes in drinking at 30 and 60 days.
This intervention resulted in a decrease in the number of drinks per day
at 30 and 60 days (from 3.2 drinks per day at baseline to 1.7 drinks at
30 days and 1.2 drinks at 60 days). The IVR system was utilized; 77
percent of all possible daily calls were completed at 30 days. However,
these improvements can not be attributed to the intervention with
confidence because there was no control group.

Parsons and Colleagues (2007) Study. These investigators conducted
an RCT among 143 HIV-infected people with "hazardous drinking"
(defined as more than 16 standard drinks per week for men or more than
12 standard drinks per week for women), assessing treatment effects on
HIV medication adherence and alcohol outcomes. The intervention involved
eight 1-hour individual sessions of MI and cognitive behavioral skills
training over 3 months and was compared with a time- and
content-equivalent control. (4) Over the follow-up period (3 and 6
months), both groups exhibited substantial improvement for both total
alcohol drinks over 14 days or drinks per drinking day, although no
significant differences existed between the intervention and the control
group. However, compared with the control group, the intervention did
improve medication adherence, number of virus particles detectable in
the blood (i.e., viral load), and CD4 cell (5) counts at 3 months. These
statistically significant improvements were not sustained at 6 months.

Samet and Colleagues (2005) Study. This RCT included 151
HIV-infected patients on antiretroviral therapy (ART) who had a history
of alcohol problems. The participants received either four
nurse-delivered, 30- to 60-minute sessions focusing on HIV medication
adherence and alcohol counseling, both in a clinic and at home, or no
intervention. The study found no significant differences between groups
upon examination of the following outcomes: 3-day medication adherence,
30-day adherence, CD4 cell count, viral load, drinks per day, percent
reporting drinking, or percent reporting hazardous drinking. Study
limitations were that not all participants were non-adherent to their
HIV medication at baseline and a substantial percentage were not in the
risky-drinking range of unhealthy alcohol use, the group most amenable
to brief interventions.

CLINICAL TRIALS AMONG HIV-INFECTED PEOPLE OF WHOM AT LEAST 10
PERCENT CURRENTLY USE ALCOHOL

Five studies identified in the literature review fell into this
category, and only one of these (Rotheram-Borus et al. 2009)
demonstrated significant treatment effects on alcohol use (see table 1).
This study was a subanalysis of a parent RCT among 936 HIV-infected
people who were sexually active without a condom with at least one
HIV-negative partner or two HIV-infected partners (Wong et al. 2008).
The participants received either 15 90-minute individual sessions of
cognitive-behavioral therapy (CBT) delivered over 15 months or usual
care. The subanalysis by Rotheram-Borus and colleagues (2009) was
limited to 270 HIV-infected participants who were homeless or without
stable housing. In this group, the intervention was found to reduce
alcohol or marijuana use from 36 to 28 days in the prior 90 days,
whereas in the control group the frequency of alcohol or marijuana use
was unchanged at 35 of the last 90 days. However, this study had
substantial methodological limitations, some of which pertain to the
parent study. For example, in the parent study, random assignment of
participants to the groups resulted in an imbalance between the groups
with respect to baseline HIV risk behaviors or demographics. Moreover,
the sub analysis was limited to participants who completed four
follow-ups and were homeless or without stable housing. Finally, the
outcome was alcohol or marijuana use in the last 3 months with no
alcohol-specific results provided.

The four other studies in this category did not demonstrate any
significant effects of the interventions tested on alcohol use:

* In a preliminary analysis of 3-month outcomes among 51 subjects
randomized to four 1-hour motivational enhancement therapy sessions in
an adolescent clinic, Naar-King and colleagues (2006) observed a trend,
but no statistically significant reduction, in the number of drinks per
week during the week with the maximum number of drinks. Moreover, in the
final analysis of the study, which included 65 subjects, 39 percent of
whom used alcohol, this difference was not sustained at 6 or 9 months
(Naar-King et al. 2008).

* Gilbert and colleagues (2008) randomized 476 HIV-infected
patients, 38 percent of whom reported risky drinking, to an MI-based
"Video Doctor" intervention via laptop computer or a control
group receiving usual care. The intervention resulted in decreased
30-day illicit drug use, lower mean number of drug use days, and a
modest reduction of unprotected sex at 3 and 6 months. However, no
differences in alcohol use existed between the intervention and control
groups.

* Sorensen and colleagues (2003) randomly assigned HIV-infected
patients with drug dependence, 61 percent of whom reported current
alcohol use, to 1 year of continuous case management or to a brief
contact (i.e., one HIV risk education session and printed information).
No differences were noted in alcohol outcomes at 6, 12, or 18 months.

* A study among HIV-infected youths compared the effects of 23
2-hour group sessions and usual care on risk behaviors (Rotheram-Borus
et al. 2001). The investigators found no changes from baseline on a
measure reflecting alcohol and marijuana use and no difference between
the intervention and control groups.

RCTS AMONG ALCOHOL USERS AT HIGH-RISK FOR HIV INFECTION

Two informative RCTs have been conducted among alcohol drinkers at
high risk for HIV infection. Morgenstern and colleagues (2007) performed
a study with 198 high-risk, HIV-negative men who had sex with men and
who were diagnosed with alcohol abuse or dependence but were seeking to
moderate their alcohol use. The investigators compared the effects of 12
weekly MI sessions augmented with CBT with 4 sessions of MI alone.
Unexpectedly, the investigators found that the nonaugmented MI group had
less drinking and fewer alcohol-related drinking problems than the
MI-plus-CBT group during the 12 weeks of the intervention and that there
were no significant differences at 12-month follow-up. Thus, the
addition of CBT to MI techniques provided no additional benefit
regarding alcohol outcomes and potentially even diminished effects in
this population. Subgroup analyses demonstrated that the detrimental
effect of augmentation occurred particularly in participants with a
concomitant drug use disorder.

Another RCT (Kalichman et al. 2008) compared a 3-hour, skills-based
HIV and alcohol risk reduction group session with a 1-hour HIV/alcohol
information group session among 342 South Africans frequenting drinking
establishments. In this study, the extended session resulted in
decreases in alcohol use before sex and unprotected intercourse at 3
month but not at 6 month follow-up. Moreover, intervention effects were
stronger in participants drinking less at baseline.

DISCUSSION

Given the high prevalence of unhealthy alcohol use among
HIV-infected people and its associated adverse health consequences,
development of clinical and public health interventions that seek to
address alcohol use and improve health outcomes in this population is a
priority. In recognition of this, NIAAA, as early as 1996, issued a
request for applications entitled "Developing Alcohol-Related HIV
Preventive Interventions (AA-97 -03)." Since then, several studies
have been published that describe clinical outcomes of interventions in
this population. However, as this article has demonstrated, the
literature on this important topic still is not extensive. A literature
search revealed only four clinical intervention studies focusing
exclusively on HIV-infected patients with current or past unhealthy
alcohol use; five other clinical trials included and documented the
alcohol use of some of their HIV-infected participants. Overall, the
current state of research strongly suggests that although the problems
related to alcohol in HIV-infected people are abundant, effective
interventions are few and new ones are urgently needed. Hence,
addressing alcohol problems remains an important issue in HIV research.

Not only are studies among alcohol-abusing, HIV-infected patients
scarce, but the existing studies also yielded mixed results. Two of the
four studies that specifically targeted HIV-infected people with alcohol
problems showed improvement in drinking outcomes. Velasquez and
colleagues (2009) demonstrated reduced drinking levels over 12 months
after an intervention that included both MI and peer support. The
intervention was particularly strong in reducing same-day drinking and
sex, which compels further research on interventions targeting alcohol
use at the time of HIV risk behaviors (Velasquez et al. 2009). Although
the intervention types used in the study only were shown to be effective
in a sample of men who have sex with men, they warrant study among other
populations. In the other study, Aharanovich and colleagues (2006)
demonstrated the feasibility of ongoing telephone-based interactive
voice response and graphic feedback, which should inspire the inclusion
of automated, tailored, ongoing intervention boosting as part of
behavioral interventions. It is important to note, however, that both
these studies had methodological limitations (e.g., substantial or
differential loss to follow-up, incomplete assessments) and their
findings therefore are not definitive. Nevertheless, they provide some
guidance for future more rigorous clinical trials.

The other two clinical trials (Parsons et al. 2007; Samet et al.
2005) among alcohol-abusing HIV-infected people attempted to improve ART
adherence. This is an appropriate target of alcohol intervention studies
in this population because medication adherence is of utmost importance
for achieving good HIV disease outcomes, and alcohol-using patients have
been documented to exhibit suboptimal ART adherence (Braithwaite et al.
2005; Chander et al. 2006; Conen et al. 2009; Samet et al. 2004). The
results of both of these trials are discouraging, however, because
although they explicitly addressed both alcohol use and medication
adherence, one study (Samet et al. 2005) found no impact on adherence,
alcohol consumption, or any HIV outcome, and the other (Parsons et al.
2007) only detected short-lived improvements (i.e., they were evident at
3 months, but not at 6 months). Thus, these two high-quality studies
suggest that achieving clinically beneficial outcomes in HIV-infected
people with alcohol problems is more difficult than has been the case
with populations of HIV-infected without diagnosed unhealthy alcohol use
(Amico et al. 2006; Simoni et al. 2006). Among the latter group, RCTs to
improve adherence that used interventions with a range of intensities
did reveal improvements in adherence which were sustained for up to 12
months, as well as in HIV viral load and CD4 counts (Tuldra et al.
2000). The difficulty of achieving positive benefits (e.g., improved ART
adherence) through interventions among HIV-infected people who have
alcohol problems also is evidenced by the study by Kalichman and
colleagues (2008) among drinkers who were not infected with HIV. The
findings of that study suggest that, as in brief intervention studies,
intervention effectiveness varies by severity of alcohol use, with less
improvement noted in dependent than in nondependent drinkers. Thus,
levels of alcohol consumption, alcohol use disorder severity, and
alcohol-related consequences are important covariates to be assessed and
reported in HIV intervention studies.

A notable finding of this literature review was that as of 2009, no
study of pharmacotherapy for alcohol dependence in HIV-infected patients
had been published. This is surprising given that pharmacotherapy plays
a major role in addressing the AIDS epidemic by improving outcomes of
HIV-infected subjects. Moreover, some preclinical research has
demonstrated that naltrexone, an effective medication for alcohol
dependence, inhibits alcohol-mediated enhancement of HIV infection (Wang
et al. 2006) and may potentiate the anti-HIV effects of antiretroviral
medications (Gekker et al. 2001). Therefore, testing the effectiveness
of naltrexone and other medications in alcohol-dependent HIV-infected
patients is an important current research direction.

Two of the studies reviewed here that included HIV-infected
patients among whom at least 10 percent currently used alcohol, targeted
risky sexual behaviors rather than alcohol consumption. Assessing
treatment effects on sex risk factors is appropriate for studies among
HIV-infected drinkers because several studies have demonstrated an
association between alcohol use and risky sex (Purcell et al. 2001;
Stein et al. 2009). In both the study by Gilbert and colleagues (2008)
and the study by Naar-King and colleagues (2006, 2008), sex risk
behaviors were decreased in the group randomized to the intervention at
3 and 6 months, but there were no or only transient effects on alcohol
use. These findings suggest that behavioral interventions which are not
specifically tailored to address alcohol use are unlikely to impact
alcohol problems in a sustained fashion.

The dearth of studies focusing on alcohol consumption among
HIV-infected people is understandable. Although the spectrum of
unhealthy alcohol use ranging from risky use to alcohol dependence
occurs in this population, other pressing health concerns (e.g., ART
adherence, risky sexual behaviors, or engagement in HIV care)
appropriately become the main focus of clinical trials that also may
address alcohol consumption in their intervention arms. Developing
interventions that target a specific behavior (e.g., sex) at the time of
alcohol use is a worthy pursuit, and understanding the importance of
decreasing alcohol use in order to successfully achieve behavior change
is crucial for developing future interventions.

One interesting development noted in the studies reviewed here was
the use of new technology (e.g., interactive voice-response systems) in
two of the studies (Aharonovich et al. 2006; Gilbert et al. 2008). These
approaches to delivering a behavioral intervention merit further
exploration because they have the potential for providing scalable,
ongoing delivery of tailored automated messages that may boost a more
intensive directly administered intervention.

When assessing the relevance of the studies reviewed here,
particularly those conducted among HIV-infected patients with past or
current unhealthy alcohol use, it is important to consider the
methodological quality of the work (i.e., the potential for bias, design
limitations, and outcome measures). The report by Velasquez and
colleagues (2009) is the only controlled study demonstrating a sustained
clinically significant treatment effect on an alcohol-specific outcome,
making publication bias (i.e., the preferential publication of studies
that find significant differences) unlikely.

Regarding their design, most, but not all, of these studies met
important design criteria, such as random allocation of participants to
treatment groups and intention-to-treat analyses (6) in the presentation
of results. As with all behavioral intervention studies, keeping
participants in the dark about which treatment they receive (i.e.,
blinding of participants to their treatment) is not possible. However,
both Parsons and colleagues (2007) and Gilbert and colleagues (2008)
utilized time- and content-equivalent controls to allow for the
detection of effects specific to the counseling method studied.

The outcome measures reported were not consistent across studies
and not always meaningful, limiting the comparability of study outcomes.
For example, Naar-King and colleagues (2006) used an alcohol-specific
measure--the number of drinks per week during the week with the maximum
number of drinks at 3 months--that is not widely used and of
questionable clinical meaning. Sorensen and colleagues (2003) only
report a measure called the Addiction Severity Index Alcohol Composite
Score, without any explanation or reporting of the individual
components, complicating judgment of its clinical meaning. Finally,
Samet and colleagues (2005) focused on ART adherence as an outcome, yet
this study may underestimate the effectiveness of the intervention
because the criteria for eligibility to participate in the study did not
exclude patients with already good adherence. Thus, participants with
good adherence at baseline provided little opportunity for an
intervention to reveal a clinically meaningful impact.

In summary, as of 2009 the medical literature on clinical trials
focused on people with HIV infection and unhealthy alcohol use is
limited (i.e., "drops in a bottle"). Few of these studies were
able to document improved outcomes, and any effects observed generally
were modest and transitory. Based on these findings and current
knowledge, the following questions need to be addressed:

* What are the characteristics of interventions that mitigate the
health consequences of alcohol use in HIV-infected people?

* How does the treatment setting impact the effectiveness of
behavioral interventions?

* How can technology best be used to extend and enhance
intervention effects?

* How can individual, network, or community interventions in people
with multiple overlapping problems, including alcohol use, optimally
reduce unhealthy behaviors?

* How might combined pharmacotherapy and behavioral therapy be
utilized to address the spectrum of clinical consequences that accompany
heavy alcohol consumption?

Obtaining answers to these questions is the key next step in the
successful development of clinical and public health interventions to
mitigate the adverse outcomes from alcohol use in HIV-infected patients.

ACKNOWLEDGEMENTS

The authors acknowledge Victoria Churchill, M.P.H, for her
thoughtful assistance in the preparation of this manuscript and Carly
Bridden, M.A., M.P.H. for reviewing the manuscript.

GALVAN, F.H.; BING, E.G.; FLEISHMAN, J.A.; ET AL. The prevalence of
alcohol consumption and heavy drinking among people with HIV in the
United States: Results from the HIV Cost and Services Utilization Study.
Journal of Studies on Alcohol 63:179-186, 2002. PMID: 12033694

Institute of Medicine. Broadening the Base of Treatment for Alcohol
Problems: Report of a Study by a Committee of the Institute of Medicine
Division of Mental Health and Behavioral Medicine. Washington, DC:
National Academy Press, 1990.

(1) According to the National Institute on Alcohol Abuse and
Alcoholism (2007), women who drink more than 3 drinks per day or more
than 7 drinks per week and men who drink more than 4 drinks per day or
more than 14 drinks per week are at increased risk for alcohol-related
problems. Alcohol consumption levels above these limits are considered
risky drinking.

(2) RCTs are clinical studies in which patients randomly are
assigned to either one or more groups receiving the treatment under
investigation or to a control group receiving no treatment or a
treatment of known efficacy.

(3) The transtheoretical model (TTM) is a health behavior theory
that assesses the individual's readiness to change a particular
behavior in order to facilitate the desired behavior change. The stages
of change are: precontemplation, contemplation, preparation, action, and
maintenance.

(4) With a time- and content-equivalent control group, participants
in that group spend the same amount of time with a health care
provider/therapist as the intervention group, and they receive the same
type of information. The only difference between the intervention and
control groups is the method used to deliver the information, allowing
researchers to determine whether one approach is more effective than the
other.

(5) CD4 cells are a type of white blood cell that is the main
target of the HIV virus; accordingly, levels of these cells in the blood
decline with progressing HIV infection and are a marker for disease
progression.

(6) An intention-to-treat analysis is based on the initial
treatment intent, not on the treatment actually administered. Thus,
every participant who begins the treatment is considered to be part of
the trial, whether they finish it or not. This is done to avoid various
misleading artifacts that can arise in a study. For example, if
participants who have a more serious problem tend to drop out at a
higher rate, even an ineffective treatment may appear to provide
benefits if one only compares the condition before and after the
treatment among participants who finish the treatment and ignores
participants who were enrolled originally but did not finish the
treatment.

JEFFREY H. SAMET, M.D., M.A., M.P.H., is a professor in the
Clinical Addiction Research and Education (CARE) Unit, Section of
General Internal Medicine, Department of Medicine, Boston University
School of Medicine, and in the Department of Social and Behavioral
Sciences, Boston University School of Public Health, both in Boston,
Massachusetts.

ALEXANDER Y. WALLEY, M.D., M.SC., is an assistant professor in the
CARE Unit, Section of General Internal Medicine, Department of Medicine,
Boston University School of Medicine, Boston, Massachusetts.

Table 1 Studies Identified During a Literature
Search on Interventions to Decrease Alcohol Use
and Related Behaviors among HIV-Infected People
and Alcohol Users at High Risk for Infection
Study Population/Setting
Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use
Velasquez Population: 253
et al. 2009 HIV-infected men
who had sex with men
(MSM) in the previous 3
months and an AUDIT
score of more than 8.
Setting: Recruited from
HIV organizations,
advertising, and
social venues
between 1999 and
2003.
Aharonovich Population: 31
et al. 2006 HIV-infected men and
women engaged in
HIV primary care.
Alcohol use: All had
four or more drinks
at least once in the
past 30 days, 55%
had five or more
drinks in the last
week.
Setting: HIV primary
care clinic.
Parsons Population: 143
et al. 2007 HIV-infected subjects
on antiretroviral therapy
(ART) with hazardous
drinking (more than 16
drinks per week for
men, more than 12
drinks per week for
women) recruited
through HIV clinics and
advertising from 2002
to 2005.
Setting: Behavioral
research center.
Samet Population: 151
et al. 2005 HIV-infected patients
on ART, with current
or lifetime alcohol
problems, determined
by two or more
positive responses on
CAGE questionnaire
or clinical diagnosis of
alcohol disorder
recruited from 1997
to 2000.
Setting: Hospital
(patients receiving
HIV medical care).
Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use
Rotheram- Population: 270
Borus et al. HIV-infected people
2009 sexually active without
a condom with at least
one HIV-negative
partner or two
HIV-infected partners
who were marginally
housed and had four
or more assessments;
recruited from 2000
to 2002.
Alcohol use: Mean
number of days using
alcohol or marijuana
in the last 90 was 37.
Setting: Recruited from
community agencies,
medical clinics, and
advertisements.
Naar-King Population: 65
et al. 2006, HIV-infected patients,
2008 aged 16-25 regardless
of alcohol use or risk
behaviors.
Alcohol use: 77%
lifetime, 39% had used
alcohol in last 30 days
at study entry.
Setting: Adolescent
HIV care clinic within
a tertiary care children's
hospital.
Gilbert Population: 476
et al. patients with alcohol
2008 risk (38%), defined
as exceeding NIAAA
safe drinking limits
or drug risk (42%),
or sex risk (60%),
were recruited
between 2003 and
2006.
Setting: Outpatient
HIV clinics.
Sorensen Population: 190
et al. 2003 HIV-infected patients
with substance
dependence; recruited
from inpatient medical
wards, detoxification
clinic, and the
emergency department
from 1994 to 1996.
Alcohol use: 61% in
the last 30 days.
Setting: Public general
hospital.
Study Population/Setting
Rotheram- Population: 310
Borus et al. HIV-infected patients
2001 (age 13-24) from nine
adolescent clinics
recruited from 1994
to 1996.
Alcohol use: 67%
nonabstinent at
baseline.
Setting: Adolescent
clinics.
Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection
Morgenstern Population: 198 MSM
et al. 2007 with current alcohol
user disorder.
Alcohol use: 88% with
alcohol dependence.
Mean drinks per
drinking day was 10.4.
Setting: Subjects
recruited through
advertisements in gay
media, internet chat
rooms, outreach to
gay bars and clubs.
Kalichman Population: 342 men
et al. 2008 and women who drink
in South African
shebeens.
Setting: Informal
alcohol establishments
(shebeens).
Study Design
Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use
Velasquez Intervention: Randomized
et al. 2009 Controlled Trial (RCT) of four
sessions of motivational
interviewing (MI)-based
individual counseling and
four sessions of transtheoretical
model-based peer-group
education/support.
Control: HIV and alcohol
educational materials,
resource referrals, and advice
to stop or reduce drinking.
Assessment: Baseline, 3,
6, 9, and 12 months.
Aharonovich Intervention: 30-minute MI
et al. 2006 session on reducing alcohol
use by counselor trained in
MI plus an automated daily
telephone self-monitoring
interactive voice response
(IVR) system with graphical
feedback at 30-day follow-up
meetings.
Control: No control group.
Assessment: Baseline, 30,
60, and 90 days.
Parsons Intervention: RCT of eight
et al. 2007 60-minute MI plus cognitive
behavioral skills training (CBST)
session by Masters-level
counselors.
Control: Eight 60-minute
time and content-equivalent
education sessions by health
educators.
All sessions delivered
individually in private office
over 12 weeks.
Assessment: Baseline, 3
and 6 months.
Samet Intervention: RCT of four 15-
et al. 2005 to 60-minute sessions over
3 months with MI-trained
nurse who (1) addressed
alcohol problems, (2) educated
about ART efficacy, and
(3) delivered tailored
adherence advice including a
reminder watch and a home visit.
Control: Standard care
Assessment: Baseline, 6,
and 12 months.
Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use
Rotheram- Intervention: RCT of 15
Borus et al. 90-minute individual counseling
2009 sessions, organized in three
modules ("Coping" at 0-5
months, "Act Safe" at 5-10
months, and "Stay Healthy"
at 10-15 months).
Control: No intervention, only
assessments
Assessment: Baseline, 15, 20,
and 25 months.
Naar-King Intervention: RCT of four
et al. 2006, 60-minute sessions of
2008 motivational enhancement.
Therapy focused on two of
three areas: substance use,
sexual risk, or medication
adherence over 10 weeks.
Control: Wait list and standard
care.
Assessment: Baseline, 3, 6,
and 9 months.
Gilbert Intervention: RCT of two
et al. sessions of tailored risk-
2008 reduction counseling at study
entry and 3 months using a
MI "Video Doctor" via laptop
computer, printed educational
worksheet, and delivery of
a cueing sheet on reported
risks to clinic care providers.
Control: Standard care.
Assessment: Baseline, 3,
and 6 months.
Sorensen Intervention: RCT of 12
et al. 2003 months of case management
by certified substance
counselors in the community
with caseload of 1:20
Control: Single brief contact
with education about
reducing HIV risk, information
on HIV services, referrals to
addiction treatment, social
services.
Assessment: Baseline, 6,
12, and 18 months.
Study Design
Rotheram- Intervention: 23 group
Borus et al. sessions of two modules
2001 ("Stay Healthy" and "Act
Safe").
Control: Standard care.
Eligible for receiving the
intervention at the
conclusion of the study.
Assessment: Baseline, 9,
and 15 months.
Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection
Morgenstern Intervention: 12 sessions of
et al. 2007 combined MI and coping
skills training (MI+CBT) over
12 weeks (n = 47).
Control: Four sessions of
MI over 12 weeks (n = 42).
Non-help-seeking (NHS)
control group (n = 109).
Assessment: Baseline, 12
weeks, and 12 months.
Kalichman Intervention: 3-hour skills-
et al. 2008 based HIV-alcohol risk-
reduction group session.
Control: 1-hour HIV-alcohol
information group session.
Assessment: Baseline, 3,
and 6 months.
Study Outcomes/Results
Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use
Velasquez Alcohol use: Control group
et al. 2009 had 1.38 times the number
of drinks per 30 days and
1.50 times the number of
heavy drinking days per 30
days compared with the
intervention group.
Sex risk: No significant
effect was demonstrated
for anal sex without a
condom or number of days
on which drinking and sex
occurred.
Aharonovich Drinks per day: Using 7-day
et al. 2006 recall, mean drinks per
day was 3.2 at baseline,
1.7 at 30 days, and 1.2 at
60 days. Mean highest
drinks per day was 8.4, 4.1,
and 3.8, respectively.
Cocaine use: Decreased
significantly at 60 days.
Parsons Alcohol use: No significant
et al. 2007 effects on total drinks over
14 days or drinks per drinking
day. Decreases in both
groups from baseline to 3
and 6 months for these two
drinking outcomes.
Medication adherence:
Significant improvement in
dose and day adherence
at 3 months, but difference
not retained at 6 months.
HIV viral load/CD4 cell
count: Significant
improvement at 3 months
but not at 6 months.
Samet Alcohol use: No significant
et al. 2005 effects on drinks per day,
percent reporting any
drinking, percent reporting
hazardous drinking.
Medication adherence:
No significant effects on
3-day or 30-day adherence.
HIV viral load/ CD4 cell
count: No significant
effects on mean CD4 cell
count or mean log HIV RNA.
Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use
Rotheram- Alcohol or marijuana use
Borus et al. in the last 3 months: At 25
2009 months, the intervention
group reduced its use
from 36 to 28 days in the
prior 90 days, whereas
the control group was
unchanged at 35 days of
the last 90.
Number of HIV negative
partners and risky sexual
acts also was reduced.
Naar-King No significant effects at
et al. 2006, 9-month follow-up.
2008 Alcohol use: Borderline
significant reduction in
number of drinks in the
week containing the
maximum number of drinks
(-9.65 vs. -1.3) at 3 months
(n = 51).
Marijuana use: Borderline
significant reduction in
number of times marijuana
was used (n = 65).
Sexual risk: Borderline
significant reduction in total
number of intercourse acts
without a condom at 6
months (n = 65).
HIV viral load: Significant
reduction in log viral load at
6 months (n = 65).
Gilbert Alcohol use: No significant
et al. effects on any risky drinking
2008 or number of drinks per
week.
Drug use: Significantly
decreased 30-day illicit
drug use at 3 and 6 months
and fewer days of illicit
drug use at 6 months.
Sex risk: Significantly
decreased 3-month
unprotected sex at 3 and
6 months and fewer casual
sex partners at 6 months.
No effects on condom use.
Sorensen No outcomes showed
et al. 2003 significant change between
study groups at any time
points, except decreased
sex risk index.
Outcomes measured:
Addiction severity index
composite scores, AIDS risk
assessment scores, Beck
depression inventory, health
status questionnaire, and
support evaluation list.
Study Outcomes/Results
Rotheram- Alcohol/marijuana use:
Borus et al. 63% for attendees vs. 67%
2001 for control vs. 84% for
nonattendees at 15 months.
Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection
Morgenstern Drinks per day : At 12
et al. 2007 weeks, the MI group had
greater decreases in drinks
per day than the MI+CBT
group. This difference was
not sustained at 12 months.
Both intervention groups
had greater decreases then
the NHS group, but the
NHS group also had
substantial decreases in
drinking.
Kalichman The following behaviors
et al. 2008 were improved significantly
at 3 months among the
intervention group:
* alcohol use before sex
* unprotected intercourse
* percent of sex with condoms
* number of sex partners.
Intervention effects were
significantly stronger in
those drinking less and
dissipated at 6 months.
Study Comments
Category 1: Clinical trials among HIV-infected people with
past or current unhealthy alcohol use
Velasquez Alcohol measures:
et al. 2009 AUDIT, 90-day timeline
follow-back (TLFB) at
follow-up assessments.
Differential loss to follow-
up at 12 months (34%
in intervention group and
26% in control group). Only
95 of 118 (81%) of the
intervention group and
121 of 135 (90%) of the
control group were included
in the analyses.
Aharonovich Alcohol measures:
et al. 2006 Quantity and frequency in
past week and past month.
Qualitative assessment of
the program demonstrated
satisfaction with daily
calling and the feedback
graph.
Not a randomized
controlled trial.
Parsons Alcohol measure:
et al. 2007 Self-report 14-day TLFB
to calculate total drinks
and drinks per drinking day.
Adherence measures:
Self-report dose
adherence = number of
doses taken/number of
doses scheduled over 14
days. Self-report day
adherence = number of
days with perfect
adherence/14 days.
Samet Alcohol measures:
et al. 2005 Self-report 30-day alcohol
use from the Addiction
Severity Index.
Adherence measures:
Self-reported AIDS Clinical
Trial Group scale with
100% and 95% or more
thresholds at 3-day and
30-day adherence,
respectively.
Category 2: Clinical trials among HIV-infected people of
whom at least 10% have current alcohol use
Rotheram- Subanalysis of a clinical
Borus et al. trial (Wong et al. 2008):
2009 5% used alcohol/
marijuana in the parent
study. Proportion of
alcohol users at baseline
not presented in this study.
Parent study reported only
transmission act outcomes
and demonstrated an
effect that was not
maintained at 25 months.
Imbalance in transmission
risk acts at baseline
resulted in ineffective
randomization, thus
propensity scores were
used to adjust for imbalances.
Naar-King Alcohol and drug
et al. 2006, measures: Timeline
2008 follow-back, though time
window is not stated.
Sex risk measure:
Total number of
unprotected intercourse
acts without a condom.
Note: 3-month outcomes
on 51 subjects were
published in 2006 and 6-
and 9-month outcomes
on 65 subjects published
in 2008.
Gilbert Alcohol measures:
et al. Self-reported NIAAA risky
2008 drinking over 3 months.
Drug use measures:
Self-reported drug use
over 30 days included any
cocaine, methamphetamine,
or heroin or 3 or more days
of barbiturates, prescription
opiates, hallucinogens,
inhalants, or methylene-
dioxymethamphetamine
(MDMA).
Sorensen Summary/index
et al. 2003 score is shown without
explanation of the raw
measure.
Study Comments
Rotheram- Sequential assignment of
Borus et al. 15 youths to intervention
2001 versus control groups (not
randomized).
The reported comparisons
were attendees versus
non-attendees versus
control subjects. No
intention-to-treat analysis
was reported.
Differential loss to
follow-up. No alcohol-
specific outcome was
reported.
Category 3: Randomized controlled trials among alcohol
users at high risk for HIV infection
Morgenstern Alcohol measures:
et al. 2007 CIDI at baseline.
TLFB and short
inventory of problems
at followup.
Potential subjects with
drug use more severe
than alcohol use disorder
were excluded. Less than
10% HIV infected.
Subjects lost to follow-up
not included in the
analysis.
Kalichman
et al. 2008 Alcohol measures: AUDIT,
frequency of drinking
before sex in previous
month. Change in AUDIT
scores not reported.
7% HIV infected in
intervention group. 4% HIV
infected in control group.
Table 2 Studies Identified but not Selected for the Literature Review
Citation Population Reason Excluded
Golin et 140 HIV-infected No data on the proportion
al. 2003 patients. Setting: of drinkers at baseline.
Hospital HIV clinic.
Goujard et 326 HIV-infected No specific alcohol
al. 2003 patients. outcomes; alcohol group
Setting: Hospital--and not analyzed
university-based centers. independently.
Jones et 174 women with AIDS from No alcohol-specific
al. 2003 three U.S. cities outcomes reported.
recruited in 1997 from
outpatient clinics,
community health centers
and agencies, and
participant referrals.
Alcohol use: 32% with
history of alcohol.
Setting: Primarily
recruited from outpatient
clinics, community health
centers, and participant
referrals.
Pradier et 244 HAART-treated No specific alcohol
al. 2003 patients. outcomes; alcohol group
Setting: Hospital not analyzed
independently.
Samet et 181 Russian men and women No alcohol-specific
al. 2008 who reported any alcohol outcomes reported.
or drug dependence and Although both HIV-
who reported at least one infected and alcohol-
incidence of unprotected dependent patients were
sex in the past 6 months. included in this study,
the HIV-infected patients
Setting: Narcology were not the alcohol-
hospitals dependent patients.
Sampaio- 107 HIV-infected, Alcohol-specific outcomes
Saet al. antiretroviral-naive not reported.
2008 patients at an Brazilian
HIV clinic for whom
antiretrovirals were
indicated were recruited
from 2003 to 2004. 45%
with alcohol use in the
last 3 months.
Simoni et 136 HIV-infected men and No information on current
al. 2007 women. use; no specific alcohol
outcomes.
Setting: Outpatient
clinic
Wong et 936 HIV-infected from Alcohol-specific outcomes
al. 2008 four U.S. cities not reported; absolute
recruited between 2000 numbers for outcome not
and 2002. presented.
Setting: Community
agencies, AIDS service
organizations, and
medical clinics
SOURCES: Golin, C.E.; Earp, J.; Tien, H.C.; et al. A 2-arm,
randomized, controlled trial of a motivational interviewing-
based intervention to improve adherence to antiretroviral
therapy (ART) among patients failing or initiating ART.
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2006; Goujard, C.; Bernard, N.; Sohier, N.; et al. Impact of
a patient education program on adherence to HIV medication:
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Deficiency Syndromes 34:191-194, 2003; Jones, D.L.; Ishii,
M.; LaPerriere, A.; et al. Influencing medication adherence
among women with AIDS. AIDS Care 15:463-474, 2003; Pradier,
C.; Bentz, L.; Spire, B.; et al. Efficacy of an educational
and counseling intervention on adherence to highly active
antiretroviral therapy: French prospective controlled study.
HIV Clinical Trials 4:121-131, 2003; Samet, J.H.; Krupitsky,
E.M.; Cheng, D.M.; et al. Mitigating risky sexual behaviors
among Russian narcology hospital patients: The PREVENT
(Partnership to Reduce the Epidemic Via Engagement in
Narcology Treatment) randomized controlled trial. Addiction
103:1474-1483, 2008; Sampaio-Sa, M.; Page-Shafer, K.;
Bangsberg, D.R.; et al. 100% adherence study: Educational
workshops vs. video sessions to improve adherence among ART-
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12:S54-S62, 2008; Simoni, J.M.; Pantalone, D.W.; Plummer,
M.D.; and Huang, B. A randomized controlled trial of a peer
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and women. Health Psychology 26:488-495, 2007; Wong, F.L.;
Rotheram-Borus, M.J.; Lightfoot, M.; et al. Effects of
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